Addiction

Cocaine, especially crack, can hook some users on the first try; anyone can become addicted after repeated use.

In scientific studies, rats or monkeys are hooked up to an intravenous source of the drug being studied. If the drug is heroin, the animals will self-administer it indefinitely, but they do still sleep and eat. Rats or monkeys who can self-administer cocaine, however, will do virtually nothing else. They even stop eating and sleeping. They continue to push their drug-delivery lever for as long as they are physically capable of doing so. Within weeks, if not days, they lose a substantial portion of their body weight, up to 40%. Within a month, they are dead.

Cocaine-addicted rats become excited when they simply see the lever that selects cocaine. It's called an addiction "cue." Human cocaine addicts have cues too. They may have a racing heartbeat when they see the things that go with taking cocaine, like large amounts of cash, straws, or crack pipes. Even recovered cocaine addicts - people who haven't used in years -- will often have intense cravings when they pass by a place where they used cocaine or they hear someone talk about using.

With respect to cocaine addiction, scientists have recently isolated a brain protein called delta-FosB (pronounced "fawz-bee") that builds up in a cocaine abusers' brain and changes its functioning, maybe forever. The protein isn't produced in the brain until someone has used cocaine for a while. Once the buildup begins, the need for the drug becomes overpowering and the user's behavior becomes increasingly compulsive. ``It's almost like a molecular switch,'' said Eric Nestler, who led the research into delta-FosB. ``Once it's flipped on, it stays on, and doesn't go away easily.''

Withdrawal

After the drug-fueled high comes the crash. The crash involves anxiety, depression, irritability, extreme fatigue and paranoia. Physical health may deteriorate. An intense craving for more cocaine develops. Stereotyped compulsive and repetitive patterned behavior may occur, meaning that the person will repeat certain odd physical movements over and over. Many addicts experience tactile hallucinations of insects crawling underneath the skin ("formication.") Severe depressive conditions, agitated delirium and a syndrome known as toxic paranoid psychosis may follow.

Addiction Studies

A Protein Key To Cocaine Addiction

Scientists have found a key to cocaine addiction that may point toward more effective treatments. The key is a protein that functions almost as a "switch" that turns on the uncontrollable cravings of drug addicts.

The protein of interest is called delta-FosB, Researchers have known for some time that prolonged use of cocaine increases the production of this protein in the nucleus accumbens, a region of the brain important for the perception of pleasure. The study showed prolonged use of cocaine, amphetamines, morphine, nicotine and PCP triggers the production of delta-FosB. Delta-FosB then activates a gene that produces components of various neurotransmitters, such as dopamine and serotonin.

The lead researcher on the study, Eric Nestler, says, "By discovering a role for delta-FosB, we can now try to intervene either at the level of delta-FosB - or of any of its relevant target genes - to perhaps arrest or reverse the addiction process."

One recent study identified more than 400 human genes that are affected by long-term cocaine abuse. This discovery represents the first molecular profile, or fingerprint, for human drug addiction and ultimately could lead to new treatments for addiction. The genes in question seem to be been either turned "on" or "off" due to long-term cocaine use; they are "disregulated" by the drug.

Scientists expect to find more cocaine-disregulated genes, and hope to study which genes are not disregulated by the drug and why. The author of the study, Dr. Hemby , says that it now appears that genes form the biological underpinnings for addiction. Understanding the mechanisms at the gene level could allow the development of addiction treatments. However, Dr. Hemby adds, "It isn't reasonable to believe that we can cure cocaine addicts," he says. "Any therapeutic approach should instead be designed to prevent relapse."

Two 1998 studies suggest that the popular hypothesis for how cocaine works in the brain is incomplete. For 30 years, researchers have theorized that dopamine, a brain chemical involved in sensations of reward and pleasure, is required for cocaine addiction. These studies used "knockout mice" - mice with a specific gene removed before birth - to show that the neurotransmitter serotonin may also play a large role in cocaine addiction.

Without the "dopamine transporter" gene, the knockout mice should not have wanted cocaine and should not have self-administered it. The flood of dopamine in their brains caused by the lack of a dopamine transporter should have made them feel "coked up" without the cocaine. But the animals did continue to give themselves cocaine anyway, leading the researchers to the serotonin transmission hypothesis.

A follow-up study used mice with a serotonin receptor called 1B "knocked out." These mice also rapidly learned to inject themselves repeatedly with cocaine. Their brains seemed to be compensating for the absence of the serotonin 1B receptor. It appeared after further study that the mice had high levels of the protein delta-FosB, which in normal mice is only found in high amounts after the animal has been given chronic doses of cocaine. In other words, these knockout mice were born as if addicted to cocaine.

Two 1998 studies suggest that the popular hypothesis for how cocaine works in the brain is incomplete. For 30 years, researchers have theorized that dopamine, a brain chemical involved in sensations of reward and pleasure, is required for cocaine addiction.

These studies used "knockout mice" - mice with a specific gene removed before birth - to show that the neurotransmitter serotonin may also play a large role in cocaine addiction. Without the "dopamine transporter" gene, the knockout mice should not have wanted cocaine and should not have self-administered it. The flood of dopamine in their brains caused by the lack of a dopamine transporter should have made them feel "coked up" without the cocaine. But the animals did continue to give themselves cocaine anyway, leading the researchers to the serotonin transmission hypothesis.

A follow-up study used mice with a serotonin receptor called 1B "knocked out." These mice also rapidly learned to inject themselves repeatedly with cocaine. Their brains seemed to be compensating for the absence of the serotonin 1B receptor. It appeared after further study that the mice had high levels of the protein delta-FosB, which in normal mice is only found in high amounts after the animal has been given chronic doses of cocaine.In other words, these knockout mice were born as if addicted to cocaine.

Various researchers have examined the idea that some drug addicts and alcoholics become addicted in a subconscious effort to "treat" their psychiatric illnesses. Psychiatric disorders, particularly the disorders having to do with mood, seem to increase a person's risk of developing stimulant abuse. Psychoactive drugs interact with the individual's own psychiatric disturbances and painful emotional states. These people become addicted to cocaine and suffer the same devastating health damage as other addicts.

If the underlying psychiatric illness is diagnosed, it can be treated with appropriate medications. When the psychiatric illness is under control, the addiction can often be resolved. Even though depression is readily treatable with highly effective pharmaceutical drugs, some individuals with major depression choose to abuse cocaine to "self-medicate." Those individuals may experience some relief of fatigue and low mood. Others have increased feelings of self esteem, assertiveness, and frustration tolerance, among other symptoms. Another group of people who often select cocaine as their drug of abuse are those with attention-deficit hyperactivity disorder (ADHD,) who experience less impulsive or hyperactive behavior. Individuals with ADHD seem to have a "paradoxical" (opposite to the usual) response to cocaine that allows them to feel more calm than they otherwise feel.

It also appears that some with cyclical mood disorders (bipolar or manic depressive disorder, cyclothymic disorders) may select stimulants like cocaine over other substances of abuse.